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Japanese Phase II Study of SB-497115-GR in Hepatitis C Virus Infected Patients

Primary Purpose

Hepatitis C, Chronic

Status

Completed

Phase

Phase 2

Locations

Japan

Study Type

Interventional

Intervention

SB-497115-GR

About this trial

This is an interventional treatment trial for Hepatitis C, Chronic focused on measuring Thrombocytopenia, Hepatitis C, chronic

Eligibility Criteria

20 Years - 74 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subject is able to understand and comply with protocol requirements and instructions and is likely to complete the study as planned, as well as provided a written consent.

A subject age between ≥20 and <75 years at time of informed consent.
A subject who applies to one of the following:

Female subject with non-childbearing potential [i.e., physiologically incapable of becoming pregnant, who: has had a hysterectomy, or had a bilateral oophorectomy (ovariectomy), or had a bilateral tubal ligation, or is post-menopausal for greater than one year].

Female subject with childbearing potential, has a negative urine or serum pregnancy test at screening and within the 24-hour period prior to the first dose of SB-497115-GR, and completely abstains from intercourse or agree to use two of the following acceptable methods of contraception for 14 days before exposure to SB-497115-GR, throughout the clinical trial, and for 24 weeks after completion or premature discontinuation from the study.

Intrauterine device or intrauterine system that meets the effectiveness criteria as stated in the product label.

Male partner sterilization prior to the female subject's entry into the study, and this male is the sole partner for that subject.

Double-barrier contraception (condom with spermicidal jelly, or diaphragm with spermicide).

Male subject with childbearing potential partner completely abstains from intercourse or agree to use condom and diaphragm with spermicide.

Subjects who were diagnosed as hepatitis C or compensated liver cirrhosis (Child-Pugh class A) without hepatic encephalopathy, or ascites. If there is a clear cirrhosis, treatment should be given with care as there is a potential of progressing to liver failure.
Subjects who, in the opinion of the investigator, are appropriate candidates for Peg-IFN and RBV combination therapy for 48 weeks.
HCV positive by TaqMan test at screening.
Subject who fulfil all the organ functions below.

Items Values Platelet <80,000 /μL Haemoglobin ≥12.0 g/dL* Absolute neutrophil count (ANC) ≥1500 /μL* Creatinine clearance >50 mL/minute Total bilirubin <2.0 mg/dL Albumin >3.0 g/dL Prothrombin time >60%

*If the investigators consider the values are sufficient to give Peg-IFN/RBV, then a subject can be enrolled upon consulting the Medical Monitor.

Exclusion Criteria:

Subject who relapsed or did not respond after 48 weeks of Peg-IFN/RBV therapy had been given with sufficient dose previously.
Subject with history of IFN (including Peg-IFN) therapy or Peg-IFN/RBV therapy, but could not been treated with optimal Peg-IFN/RBV therapy due to the reasons other than thrombocytopenia.
Subject who received IFN therapy (including Peg-IFN), antiviral therapy (excluding oseltamivir phosphate, etc.), immuno-modulatory treatment, radiotherapy or phlebotomy within 3 months (90 days) prior to the first dose of SB-497115-GR.
Treatment with an investigational drug within 30 days prior to the first dose of SB-497115-GR or 5 half-lives of that investigational drug (whichever is longer).
Subject with decompensated liver disease.
Chronic liver disease other than chronic hepatitis C (e.g., autoimmune hepatitis, alcohol-induced hepatitis, drug-induced hepatitis, etc.).
Subject with idiopathic thrombocytopenic purpura or active autoimmune disease.
Subject who have had a malignancy diagnosed and/or treated within the past 5 years.
Subjects who require endoscopic treatment for varices or documented history of clinically significant bleeding from oesophageal or gastric varices.
Any disease condition associated with active bleeding or requiring anticoagulation with heparin or warfarin.
Subject with serious cardiac, cerebrovascular, chronic pulmonary disease or interstitial lung disease, or documented history of any of these diseases.
Pre-existing cardiac disease (congestive heart failure in New York Heart Association Grade III/IV), or arrhythmias known to involve the risk of thromboembolic events (e.g. atrial fibrillation), or subjects with a QTcF >450 msec or if with bundle brunch block, QTcF >480 msec.
Subject with depression, psychiatric disorder requiring treatment or suicidal ideation or suicide attempt history, or history of these.
Subject with uncontrolled hypertension (≥160 mmHg systolic or ≥100 mmHg diastolic).
Subject with diabetes mellitus that can not be controlled by treatment.
Thyroid dysfunction not adequately controlled.
Subjects with haemoglobinopathies.
History or current condition of seizure disorder.
Subject who was positive for Human Immunodeficiency Virus (HIV) antibody or Hepatitis B Virus (HBV) antigen.
Subject with arterial or venous thrombosis history or evidence of portal vein thrombosis on abdominal imaging (e.g., by computerized tomography or magnetic resonance imaging) within 3 months.
History of alcohol/drug abuse or dependence.
History of platelet clumping that prevents reliable measurement of platelet counts.
Subjects planning to have cataract surgery.
History of major organ transplantation.
Known hypersensitivity to SB-497115-GR ingredients, IFN (including Peg-IFN), nucleoside analogues or biological agents (i.e., vaccines).
Pregnant or nursing women or a male subject with pregnant partner.

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

SB-497115-GR

Arm Description

investigational product for thrombocytopenia

Outcomes

Primary Outcome Measures

Number of Participants Whose Platelet Count Increased From a Baseline Count of < 80 Gi/L to a Count >=100 Gi/L During Part 1

Participants were assessed for a shift from a baseline platelet count of <80 Gi/L to a count >=100 Gi/L during Part 1(up to 9 weeks). Platelet counts were measured by blood draw.

Number of Participants Whose Platelet Counts Maintained at >=50 Gi/L During Part 2

Participants were assessed for continuously maintaining platelet counts >=50 Gi/L during Part 2. Platelet counts were measured by blood draw.

Secondary Outcome Measures

Median Platelet Count at the Indicated Time Points in Part 1

Platelet counts were measured by blood draw

Time in Weeks to Achieve Platelet Count >= 100 Gi/L

Participants were assessed for achieving platelet counts >=100 Gi/L during Part 1. Platelet counts were measured by blood draw.

Median Platelet Count at the Indicated Time Points in Part 2

Platelet counts were measured by blood draw

Median Platelet Count at the Indicated Time Points During Follow-up Period After Part 2

Platelet counts were measured by blood draw at specified timepoints.

Minimum Platelet Count on Antiviral Therapy

Participants were assessed for platelet counts during antiviral therapy in Part 2. Platelet counts were measured by blood draw.

Dose of Eltrombopag That Enabled Initiation of Antiviral Therapy

Participants received eltrombopag at escalating dosages until a platelet count of >=100 Gi/L was achieved in Part 1. Platelet counts were measured by blood draw.

Number of Antiviral Therapy Dose Reductions in Part 2

Number of reductions in Part 2 of either Peg-IFN or RBV. Participants were assigned a score equal to the number of times antiviral therapy was reduced (0=no dose reductions [DRs]; 1=one DR; 2=two DRs; 3=three DRs; >3=more than three DRs). Where possible, every effort was made to maintain the recommended dose of antiviral therapy. However, where dose modification of antiviral therapy was required due to safety concerns, it was performed by the Investigator as per the region-specific product labels of Peg-IFN and/or RBV.

Number of Participants With the Indicated Levels of Peg-IFN Alpha-2a Therapy Dose Reductions in Part 2

Participants were assigned a score equal to the number of times their Peg-IFN alpha-2a dose of antiviral therapy was reduced (0=no dose reductions [DRs]; 1=one DR; 2=two DRs; 3=three DRs; >3=more than three DRs). Where possible, every effort was made to maintain the recommended dose of antiviral therapy. However, where dose modification of antiviral therapy was required due to safety concerns, it was performed by the Investigator as per the region-specific product labels of Peg-IFN.

Number of Participants With the Indicated Levels of Peg-IFN Alpha-2b Therapy Dose Reductions in Part 2

Participants were assigned a score equal to the number of times their Peg-IFN alpha-2b dose of antiviral therapy was reduced (0=no dose reductions [DRs]; 1=one DR; 2=two DRs; 3=three DRs; >3=more than three DRs). Where possible, every effort was made to maintain the recommended dose of antiviral therapy. However, where dose modification of antiviral therapy was required due to safety concerns, it was performed by the Investigator as per the region-specific product labels of Peg-IFN.

Number of Participants With the Indicated Levels of RBV Therapy Dose Reductions in Part 2

Participants were assigned a score equal to the number of times their RBV dose of antiviral therapy was reduced (0=no DRs; 1=one DR; 2=two DRs; 3=three DRs; >3=more than three DRs). Where possible, every effort was made to maintain the recommended dose of antiviral therapy. However, where dose modification of antiviral therapy was required due to safety concerns, it was performed by the Investigator as per the region-specific product labels of RBV

Time to First Dose Reduction of Antiviral Therapy in Part 2

Time to first dose reduction was calucated as the time period from the first dose to the first dose reduction.

Number of Participants Who Discontinued Antiviral Therapy in Part 2

Dosing discontinuation is defined as the occurrence of stopping the medication. Dosing discontinuation of Antviral Therapy was assessed up to 48 weeks in Part 2

Number of Participants Who Discontinued Peg-IFN Alpha-2a Therapy in Part 2

Dosing discontinuation is defined as the occurrence of stopping the medication. Dosing discontinuation of Peg-IFN alpha-2a therapy was assessed up to 48 weeks in Part 2

Number of Participants Who Discontinued Peg-IFN Alpha-2b Therapy in Part 2

Dosing discontinuation is defined as the occurrence of stopping the medication. Dosing discontinuation of Peg-IFN alpha-2b therapy was assessed up to 48 weeks in Part 2

Number of Participants Achieving Adherence to Antiviral Therapy in Part 2

Adherence to antiviral therapy was defined as receiving at least 80% of the prescribed dose (investigator prescribed) of Peg-IFN alfa and at least 80% of the prescribed dose (investigator prescribed) of RBV, for at least 80% of the planned duration

Number of Participants Achieving Adherence to Peg-IFN Alpha 2a Antiviral Therapy in Part 2

Adherence to antiviral therapy was defined as receiving at least 80% of the prescribed dose (investigator prescribed) of Peg-IFN alfa-2a and at least 80% of the prescribed dose (investigator prescribed) of RBV, for at least 80% of the planned duration.

Number of Participants Achieving Adherence to Peg-IFN Alpha-2b Antiviral Therapy in Part 2

Adherence to antiviral therapy was defined as receiving at least 80% of the prescribed dose (investigator prescribed) of Peg-IFN alpha-2b and at least 80% of the prescribed dose (investigator prescribed) of RBV, for at least 80% of the planned duration.

Number of Participants With Sustained Virologic Response (SVR) in Part 2

Participants with SVR were defined as those with undetectable Hepatitis C Virus (HCV) ribonucleic acid (RNA) at 24 weeks post-completion of treatment period Part 2

Number of Participants With Rapid Virological Response (RVR) and Extended RVR (eRVR) in Part 2

RVR is defined as the absence of detectable HCV RNA after 4 weeks of antiviral treatment. eRVR is defined as the absence of detectable HCV RNA between 4 weeks and 12 weeks after antiviral treatment.

Number of Participants With Early Virological Response (EVR) and Complete EVR (cEVR) in Part 2

EVR is defined as a clinically significant reduction from Baseline in HCV RNA (>=2 log10 decrease in HCV RNA or undetectable HCV RNA) after 12 weeks of antiviral treatment. cEVR, a subset of EVR, is defined exclusively as undetectable HCV RNA after 12 weeks of antiviral treatment.

Number of Participants With End of Treatment Response (ETR) for Undetectable HCV RNA at the End of Peg-IFN/RBV Treatment in Part 2

ETR is defined as undetectable HCV RNA at the end of Peg-IFN/RBV treatment.

Mean Serum HCV RNA at the Indicated Time Points In Part 2

The HCV is a small, enveloped, single-stranded, positive-sense RNA virus. Log-Transformed HCV RNA was assessed at Screening, Antiviral Baseline, Part 2 week 4, 12, 24, 36, 48 and at withdrawal.

Mean Serum HCV RNA at the Indicated Time Points During Follow-up Period After Part 2

The HCV is a small, enveloped, single-stranded, positive-sense RNA virus. Log-Transformed HCV RNA was assessed at FU Baseline, FU Week 12 and FU Week 24 during Follow-up Period after Part 2

Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE) in Part1

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death; was life threatening; required hospitalization or prolongation of existing hospitalization; resulted in disability/incapacity; was a congenital anomaly/birth defect.

Number of Participants With Any AE and Any SAE in Part 2

Number of Participants With Any AE and Any SAE During Follow-up Period After Part 2

Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 With Follow-up Period

Participant's blood pressure was measured at the indicated time points during the study. Systolic blood pressure is a measure of blood pressure while the heart is beating. Diastolic blood pressure is a measure of blood pressure while the heart is relaxed. Mean change from Baseline was calculated as the value at the indicated time points minus the value at Baseline

Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 2

Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points During Follow-up Period After Part 2

Mean Change From Baseline in Heart Rate at the Indicated Time Points in Part 1 With Follow-up Period

The heart rate was measured in participants at the indicated time points. Mean change from Baseline was calculated as the value at the indicated time points minus the value at Baseline.

Mean Change From Antiviral Baseline in Heart Rate at the Indicated Time Points in Part 2

The heart rate was measured in participants at the indicated time points. Mean change from Antiviral Baseline was calculated as the value at the indicated time points minus the value at Antiviral Baseline.

Mean Heart Rate at the Indicated Time Points During Follow-up Period After Part 2

The heart rate was measured in participants at the indicated time points.

Mean Change From Baseline in Weight at the Indicated Time Points in Part 1 With Follow-up Period

The weight of participants was recorded at the indicated time points. Mean change from Baseline was calculated as the value at the indicated time points minus the value at Baseline.

Mean Change From Baseline in Weight at the Indicated Time Points in Part 2

The weight of participants was recorded at the indicated time points. Mean change from Baseline was calculated as the value at the indicated time points minus the value at Baseline.

Mean Weight at the Indicated Time Points During Follow-up Period After Part 2

The weight of participants was recorded at the indicated time points.

Mean Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 With Follow-up Period

The Body temperature of participants was recorded at the indicated time points. Mean change from Baseline was calculated as the value at the indicated time points minus the value at Baseline.

Mean Change From Baseline in Body Temperature at the Indicated Time Points in Part 2

The Body temperature of participants was recorded at the indicated time points. Mean change from Baseline was calculated as the value at the indicated time points minus the value at Baseline

Mean Body Temperature at the Indicated Time Points During Follow-up Period After Part 2

The Body temperature of participants was recorded at the indicated time points..

Mean Change From Baseline in Body Mass Index (BMI) at the Indicated Time Points in Part 1 With Follow-up Periodc

The BMI for participants was calculated at the indicated time points as body weight in kilograms divided by height in meters squared. Mean change from Baseline was calculated as the value at the indicated time points minus the value at Baseline

Mean Change From Baseline in BMI at the Indicated Time Points in Part 2

Mean BMI at the Indicated Time Points During Follow-up Period After Part 2

The BMI for participants was calculated at the indicated time points as body weight in kilograms divided by height in meters squared.

Number of Participants With the Indicated Shift From Baseline in Severity Grades for Clinical Chemistry Parameters Per Division of Acquired Immunodeficiency Syndrome (DAIDS) in Part 1

Blood samples for the assessment of clinical chemistry parameters were taken at intervals in Part 1. Clinical chemistry parameters included albumin, alkaline phosphatase (ALP), ALT, aspartate amino transferase (AST), total bilirubin, calcium, creatinine, potassium, sodium, and uric acid. Per DAIDS toxicity table, the grade ranges for each parameter are as follows: Grade (G) 0=none, 1=mild; G2=moderate; G3=severe; G4=potentially life-threatening.

Number of Participants With the Indicated Shift From Baseline in Severity Grades for Clinical Chemistry Parameters Per DAIDS in Part 2

Blood samples for the assessment of clinical chemistry parameters were taken at intervals in Part 2. Clinical chemistry parameters included albumin, ALP, ALT, AST, total bilirubin, calcium, creatinine, potassium, sodium, and uric acid. Per DAIDS toxicity table, the grade ranges for each parameter are as follows: Grade (G) 0=none, 1=mild; G2=moderate; G3=severe; G4=potentially life-threatening.

Number of Participants With the Indicated Shift From Baseline in Severity Grades for Clinical Chemistry Parameters Per DAIDS During Follow-up Period After Part 2

Number of Participants With the Indicated Shifts From BL in Severity Grades for for Hematology Parameters Per DAIDS in Part 1

Blood samples for the assessment of hematology parameters were taken at intervals throughout the study. Participants with the worst-case shift from BL in Part 1 are reported, per severity grades by DAIDS, for levels of hemoglobin (low=anemia), lymphocytes (low=lymphocytopenia), total neutrophils (low=neutropenia), and white blood cells (low=leukocytopenia). Per the DAIDS toxicity table, grade ranges for each parameter are as follows: Grade (G) 1=mild; G2=moderate; G3=severe; G4=potentially life-threatening.

Number of Participants With the Indicated Shifts From BL in Severity Grades for for Hematology Parameters Per DAIDS in Part 2

Blood samples for the assessment of hematology parameters were taken at intervals throughout the study. Participants with the worst-case shift from BL in Part 2 are reported, per severity grades by DAIDS, for levels of hemoglobin (low=anemia), lymphocytes (low=lymphocytopenia), total neutrophils (low=neutropenia), and white blood cells (low=leukocytopenia). Per the DAIDS toxicity table, grade ranges for each parameter are as follows: Grade (G) 1=mild; G2=moderate; G3=severe; G4=potentially life-threatening.

Number of Participants With the Indicated Shifts From BL in Severity Grades for Hematology Parameters Per DAIDS During Follow-up Period After Part 2

Number of Participants With the Indicated Urinalysis Parameters Tested by Dipstick at the Indicated Time Points in Part1 With Follow Up Period

Urinalysis parameters included: urine bilirubin (UB), urine occult blood (UOB), urine glucose (UG), urine ketones (UK), pH, urine protein (UP), urine specific gravity (USG) and urine urobilinogen (UU). The dipstick test gives results in a semi-quantitative manner. UB was categorized as (-), negative (Neg). UOB was categorised as 1+, 2+, 3+, (-), Neg, trace. UG results were categorized as (-), 0.5, Neg. UK parameters were categorized as as (-), Neg. pH results were in the range of pH from 5-8.5 in increments of 0.5. UP was categorized as 1+, (-), Neg, trace. UU was categorized as 1+, 0.1, 1, 2, 4, Neg, trace, normal. USG results were in the range from 1.000-1.030 in increments of 0.001.

Number of Participants With the Indicated Urinalysis Parameters Tested by Dipstick at the Indicated Time Points in Part 2

Urinalysis parameters included: UB, UOB, UG, UK, pH, UP, USG and UU. The dipstick test gives results in a semi-quantitative manner. UB was categorized as (-), negative (Neg). UOB was categorised as 1+, 2+, 3+, (-), Neg, trace. UG results were categorized as 1+, (-), 0.5, Neg. UK parameters were categorized as as (-), Neg. pH results were in the range of pH from 5-8.5 in increments of 0.5. UP was categorized as (-), Neg, trace. UU was categorized as 1+, 0.1, 1, 2, 4, Neg, trace, normal. USG results were in the range from 1.000-1.030 in increments of 0.001.

Number of Participants With the Indicated Urinalysis Parameters Tested by Dipstick at the Indicated Time Points During Follow-up Period After Part 2

Number of Participants Assessed as Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at the Indicated Time Points

The number of participants with an ECG status of normal, abnormal, CS, or NCS, as determined by the Investigator, was reported. Normal= all ECG parameters within accepted normal ranges. Abnormal= ECG findings outside of normal ranges. CS= ECG with a CS abnormality that meets exclusion criteria. NCS= ECG with an abnormality not CS or meeting exclusion criteria, per Investigator, based on reasonable standards of clinical judgment.

Number of Participants Assessed as Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) During Follow-up After Part 2

Number of Participants With Abdominal Ultrasound With Doppler at the Indicated Time Points

Abdominal ultrasound with doppler were taken at Baseline, Week 24, Week 48, withdrawal (WD)/completion (comp). Questions were asked to assess masses suspicious for hepatocellular carcinoma (HCC), ascites, portal vein thrombosis detected, possiblility to measure spleen breadth, and other clinically significant findings (OCSF).

Number of Participants With Abdominal Ultrasound With Doppler During Follow-up Period After Part 2

Abdominal ultrasound with doppler were taken during Follow-up Period after Part 2 at FU Week 24. Questions were asked to assess masses suspicious for hepatocellular carcinoma (HCC), ascites, portal vein thrombosis detected, possiblility to measure spleen breadth, and other clinically significant findings (OCSF).

Spleen Measurements as Assessed by Abdominal Ultrasound With Doppler in the Study

Abdominal ultrasound with doppler were taken at Baseline, Week 24, Week 48, WD/comp. Questions were asked to assess masses suspicious for HCC, ascites, portal vein thrombosis detected, possiblility to measure spleen breadth, and OCSF. Spleen measurements included spleen length and spleen width (breadth).

Spleen Measurements as Assessed by Abdominal Ultrasound With Doppler During Follow-up Period After Part 2

Abdominal ultrasound with doppler were taken during Follow-up Period after Part 2 at FU Week 24. Questions were asked to assess masses suspicious for HCC, ascites, portal vein thrombosis detected, possiblility to measure spleen breadth, and OCSF. Spleen measurements included spleen length and spleen width (breadth).

Full Information

NCT ID

NCT01636778

First Posted

July 5, 2012

Last Updated

February 1, 2016

Sponsor

GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT01636778

Brief Title

Japanese Phase II Study of SB-497115-GR in Hepatitis C Virus Infected Patients

Official Title

Non-randomised, Open Label, Multi-centre Phase II Study to Assess the Efficacy and Safety of SB-497115-GR in Thrombocytopenic Subjects With Chronic Hepatitis C and Compensated Liver Cirrhosis.

Study Type

Interventional

2. Study Status

Record Verification Date

September 2015

Overall Recruitment Status

Completed

Study Start Date

July 2012 (undefined)

Primary Completion Date

May 2014 (Actual)

Study Completion Date

November 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

GlaxoSmithKline

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to assess the ability of SB-497115-GR to raise platelet counts in thrombocytopenic patients with hepatitis C virus (HCV) infection (platelet count <80,000 /μL, suggestive of compensated cirrhosis) to a level desirable to initiate antiviral therapy and to assess the ability of SB-497115-GR to maintain platelet counts at a level sufficient to minimise dose reductions of pegylated interferon (Peg-IFN) and ribavirin (RBV) therapy with the expectation that a lower rate of Peg-IFN dose reduction and omission will translate to a higher rate of sustained viral response.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatitis C, Chronic

Keywords

Thrombocytopenia, Hepatitis C, chronic

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

45 (Actual)

8. Arms, Groups, and Interventions

Arm Title

SB-497115-GR

Arm Type

Experimental

Arm Description

investigational product for thrombocytopenia

Intervention Type

Drug

Intervention Name(s)

SB-497115-GR

Intervention Description

TPO receptor agonist to increase platelet count

Primary Outcome Measure Information:

Title

Number of Participants Whose Platelet Count Increased From a Baseline Count of < 80 Gi/L to a Count >=100 Gi/L During Part 1

Description

Participants were assessed for a shift from a baseline platelet count of <80 Gi/L to a count >=100 Gi/L during Part 1(up to 9 weeks). Platelet counts were measured by blood draw.

Time Frame

From Baseline up to Week 9 in Part 1

Title

Number of Participants Whose Platelet Counts Maintained at >=50 Gi/L During Part 2

Description

Participants were assessed for continuously maintaining platelet counts >=50 Gi/L during Part 2. Platelet counts were measured by blood draw.

Time Frame

From Antiviral Baseline to up to Week 48 in Part 2

Secondary Outcome Measure Information:

Title

Median Platelet Count at the Indicated Time Points in Part 1

Description

Platelet counts were measured by blood draw

Time Frame

Baseline, Week1, 2, 3, 4, 5, 6, 7, 8, 9, Withdrawal in Part 1

Title

Time in Weeks to Achieve Platelet Count >= 100 Gi/L

Description

Participants were assessed for achieving platelet counts >=100 Gi/L during Part 1. Platelet counts were measured by blood draw.

Time Frame

From Baseline up to Week 9 in Part 1

Title

Median Platelet Count at the Indicated Time Points in Part 2

Description

Platelet counts were measured by blood draw

Time Frame

Antiviral Baseline, Week 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, Withdrawal in Part 2

Title

Median Platelet Count at the Indicated Time Points During Follow-up Period After Part 2

Description

Platelet counts were measured by blood draw at specified timepoints.

Time Frame

Follow-up (FU) Baseline, FU Week 4, FU Week 12 and and FU Week 24 after Part 2

Title

Minimum Platelet Count on Antiviral Therapy

Description

Participants were assessed for platelet counts during antiviral therapy in Part 2. Platelet counts were measured by blood draw.

Time Frame

From Antiviral Baseline to up to Week 48 in Part 2

Title

Dose of Eltrombopag That Enabled Initiation of Antiviral Therapy

Description

Participants received eltrombopag at escalating dosages until a platelet count of >=100 Gi/L was achieved in Part 1. Platelet counts were measured by blood draw.

Time Frame

From Baseline up to Week 9 in Part 1

Title

Number of Antiviral Therapy Dose Reductions in Part 2

Description

Time Frame

From Antiviral Baseline up to Week 48 in Part 2

Title

Number of Participants With the Indicated Levels of Peg-IFN Alpha-2a Therapy Dose Reductions in Part 2

Description

Time Frame

From Antiviral Baseline up to Week 48 in Part 2

Title

Number of Participants With the Indicated Levels of Peg-IFN Alpha-2b Therapy Dose Reductions in Part 2

Description

Time Frame

From Antiviral Baseline up to Week 48 in Part 2

Title

Number of Participants With the Indicated Levels of RBV Therapy Dose Reductions in Part 2

Description

Time Frame

From Antiviral Baseline up to Week 48 in Part 2

Title

Time to First Dose Reduction of Antiviral Therapy in Part 2

Description

Time to first dose reduction was calucated as the time period from the first dose to the first dose reduction.

Time Frame

From Antiviral Baseline up to Week 48 in Part 2

Title

Number of Participants Who Discontinued Antiviral Therapy in Part 2

Description

Dosing discontinuation is defined as the occurrence of stopping the medication. Dosing discontinuation of Antviral Therapy was assessed up to 48 weeks in Part 2

Time Frame

From Antiviral Baseline up to Week 48 in Part 2

Title

Number of Participants Who Discontinued Peg-IFN Alpha-2a Therapy in Part 2

Description

Dosing discontinuation is defined as the occurrence of stopping the medication. Dosing discontinuation of Peg-IFN alpha-2a therapy was assessed up to 48 weeks in Part 2

Time Frame

From Antiviral Baseline up to Week 48 in Part 2

Title

Number of Participants Who Discontinued Peg-IFN Alpha-2b Therapy in Part 2

Description

Dosing discontinuation is defined as the occurrence of stopping the medication. Dosing discontinuation of Peg-IFN alpha-2b therapy was assessed up to 48 weeks in Part 2

Time Frame

From Antiviral Baseline up to Week 48 in Part 2

Title

Number of Participants Achieving Adherence to Antiviral Therapy in Part 2

Description

Time Frame

From Antiviral Baseline up to Week 48 in Part 2

Title

Number of Participants Achieving Adherence to Peg-IFN Alpha 2a Antiviral Therapy in Part 2

Description

Time Frame

From Antiviral Baseline up to Week 48 in Part 2

Title

Number of Participants Achieving Adherence to Peg-IFN Alpha-2b Antiviral Therapy in Part 2

Description

Time Frame

From Antiviral Baseline up to Week 48 in Part 2

Title

Number of Participants With Sustained Virologic Response (SVR) in Part 2

Description

Participants with SVR were defined as those with undetectable Hepatitis C Virus (HCV) ribonucleic acid (RNA) at 24 weeks post-completion of treatment period Part 2

Time Frame

From Antiviral Baseline up to Week 48 in Part 2

Title

Number of Participants With Rapid Virological Response (RVR) and Extended RVR (eRVR) in Part 2

Description

RVR is defined as the absence of detectable HCV RNA after 4 weeks of antiviral treatment. eRVR is defined as the absence of detectable HCV RNA between 4 weeks and 12 weeks after antiviral treatment.

Time Frame

From Antiviral Baseline up to Week 48 in Part 2

Title

Number of Participants With Early Virological Response (EVR) and Complete EVR (cEVR) in Part 2

Description

Time Frame

From Antiviral Baseline up to Week 48 in Part 2

Title

Number of Participants With End of Treatment Response (ETR) for Undetectable HCV RNA at the End of Peg-IFN/RBV Treatment in Part 2

Description

ETR is defined as undetectable HCV RNA at the end of Peg-IFN/RBV treatment.

Time Frame

From Antiviral Baseline up to Week 48 in Part 2

Title

Mean Serum HCV RNA at the Indicated Time Points In Part 2

Description

The HCV is a small, enveloped, single-stranded, positive-sense RNA virus. Log-Transformed HCV RNA was assessed at Screening, Antiviral Baseline, Part 2 week 4, 12, 24, 36, 48 and at withdrawal.

Time Frame

Screening, Antviral baseline; Week 4, 12, 24, 36, 48, Withdrawal in Part 2

Title

Mean Serum HCV RNA at the Indicated Time Points During Follow-up Period After Part 2

Description

The HCV is a small, enveloped, single-stranded, positive-sense RNA virus. Log-Transformed HCV RNA was assessed at FU Baseline, FU Week 12 and FU Week 24 during Follow-up Period after Part 2

Time Frame

FU Baseline, FU Week 12 and FU Week 24 after Part 2

Title

Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE) in Part1

Description

Time Frame

From Baseline up to week 9 in Part 1

Title

Number of Participants With Any AE and Any SAE in Part 2

Description

Time Frame

From Antiviral Baseline up to Week 48 in Part 2

Title

Number of Participants With Any AE and Any SAE During Follow-up Period After Part 2

Description

Time Frame

From FU Baseline up to FU Week 24 after Part 2

Title

Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 With Follow-up Period

Description

Time Frame

Baseline; Week 1, 2, 3, 4, 5, 6, 7, 8, 9, Withdrawal in Part 1 and FU Week 4, FU Week 12, and FU Week 24

Title

Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 2

Description

Time Frame

Baseline; Antiviral Baseline,Week 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, Withdrawal in Part 2

Title

Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points During Follow-up Period After Part 2

Description

Time Frame

FU Baseline, FU Week 4, FU Week 12 and FU Week 24 after Part 2

Title

Mean Change From Baseline in Heart Rate at the Indicated Time Points in Part 1 With Follow-up Period

Description

The heart rate was measured in participants at the indicated time points. Mean change from Baseline was calculated as the value at the indicated time points minus the value at Baseline.

Time Frame

Baseline; Week 1, 2, 3, 4, 5, 6, 7, 8, 9, Withdrawal in Part 1 and FU Week 4, FU Week 12, FU Week 24

Title

Mean Change From Antiviral Baseline in Heart Rate at the Indicated Time Points in Part 2

Description

Time Frame

Antiviral Baseline, Week 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, Withdrawal in Part 2

Title

Mean Heart Rate at the Indicated Time Points During Follow-up Period After Part 2

Description

The heart rate was measured in participants at the indicated time points.

Time Frame

FU Baseline, FU Week 4, FU Week 12 and FU Week 24 after Part 2

Title

Mean Change From Baseline in Weight at the Indicated Time Points in Part 1 With Follow-up Period

Description

The weight of participants was recorded at the indicated time points. Mean change from Baseline was calculated as the value at the indicated time points minus the value at Baseline.

Time Frame

Baseline; Week 1, 2, 3, 4, 5, 6, 7, 8, 9, Withdrawal in Part 1 and FU Week 4, FU Week 12, FU Week 24

Title

Mean Change From Baseline in Weight at the Indicated Time Points in Part 2

Description

The weight of participants was recorded at the indicated time points. Mean change from Baseline was calculated as the value at the indicated time points minus the value at Baseline.

Time Frame

Baseline; Antiviral Baseline, Week 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, Withdrawal in Part 2

Title

Mean Weight at the Indicated Time Points During Follow-up Period After Part 2

Description

The weight of participants was recorded at the indicated time points.

Time Frame

FU Baseline, FU Week 4, FU Week 12 and FU Week 24 after Part 2

Title

Mean Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 With Follow-up Period

Description

The Body temperature of participants was recorded at the indicated time points. Mean change from Baseline was calculated as the value at the indicated time points minus the value at Baseline.

Time Frame

Baseline; Week 1, 2, 3, 4, 5, 6, 7, 8, 9, Withdrawal in Part 1 and FU Week 4, FU Week 12, FU Week 24

Title

Mean Change From Baseline in Body Temperature at the Indicated Time Points in Part 2

Description

The Body temperature of participants was recorded at the indicated time points. Mean change from Baseline was calculated as the value at the indicated time points minus the value at Baseline

Time Frame

Baseline; Antiviral Baseline,Week 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, Withdrawal in Part 2

Title

Mean Body Temperature at the Indicated Time Points During Follow-up Period After Part 2

Description

The Body temperature of participants was recorded at the indicated time points..

Time Frame

FU Baseline, FU Week 4, FU Week 12 and FU Week 24 after Part 2

Title

Mean Change From Baseline in Body Mass Index (BMI) at the Indicated Time Points in Part 1 With Follow-up Periodc

Description

Time Frame

Baseline; Week 1, 2, 3, 4, 5, 6, 7, 8, 9, Withdrawal in Part 1 and FU Week 4, FU Week 12, FU Week 24

Title

Mean Change From Baseline in BMI at the Indicated Time Points in Part 2

Description

Time Frame

Baseline; Antiviral Baseline,Week 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, Withdrawal in Part 2

Title

Mean BMI at the Indicated Time Points During Follow-up Period After Part 2

Description

The BMI for participants was calculated at the indicated time points as body weight in kilograms divided by height in meters squared.

Time Frame

FU Baseline, FU Week 4, FU Week 12 and FU Week 24 after Part 2

Title

Number of Participants With the Indicated Shift From Baseline in Severity Grades for Clinical Chemistry Parameters Per Division of Acquired Immunodeficiency Syndrome (DAIDS) in Part 1

Description

Time Frame

From Baseline up to Week 9

Title

Number of Participants With the Indicated Shift From Baseline in Severity Grades for Clinical Chemistry Parameters Per DAIDS in Part 2

Description

Time Frame

From Antiviral Baseline up to Week 48

Title

Number of Participants With the Indicated Shift From Baseline in Severity Grades for Clinical Chemistry Parameters Per DAIDS During Follow-up Period After Part 2

Description

Time Frame

From FU Week 4 to FU Week 24

Title

Number of Participants With the Indicated Shifts From BL in Severity Grades for for Hematology Parameters Per DAIDS in Part 1

Description

Time Frame

From Baseline up to Week 9

Title

Number of Participants With the Indicated Shifts From BL in Severity Grades for for Hematology Parameters Per DAIDS in Part 2

Description

Time Frame

From Antiviral Baseline up to Week 48

Title

Number of Participants With the Indicated Shifts From BL in Severity Grades for Hematology Parameters Per DAIDS During Follow-up Period After Part 2

Description

Time Frame

From FU Week 4 to FU Week 24

Title

Number of Participants With the Indicated Urinalysis Parameters Tested by Dipstick at the Indicated Time Points in Part1 With Follow Up Period

Description

Time Frame

Screening, Baseline, Week 1, 2, 3, 4, 7, 8, Withdrawal, FU Week 24

Title

Number of Participants With the Indicated Urinalysis Parameters Tested by Dipstick at the Indicated Time Points in Part 2

Description

Time Frame

Antiviral Baseline,Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, Withdrawal

Title

Number of Participants With the Indicated Urinalysis Parameters Tested by Dipstick at the Indicated Time Points During Follow-up Period After Part 2

Description

Time Frame

FU Baseline and FU Week 24

Title

Number of Participants Assessed as Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at the Indicated Time Points

Description

Time Frame

Screening, Antiviral Baseline, Week 12, 24, 36, 48, Withdrawal

Title

Number of Participants Assessed as Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) During Follow-up After Part 2

Description

Time Frame

FU Baseline and FU Week 24

Title

Number of Participants With Abdominal Ultrasound With Doppler at the Indicated Time Points

Description

Time Frame

Baseline; Week 24, Week 48, Withdrawal/Completion

Title

Number of Participants With Abdominal Ultrasound With Doppler During Follow-up Period After Part 2

Description

Time Frame

FU Week 24

Title

Spleen Measurements as Assessed by Abdominal Ultrasound With Doppler in the Study

Description

Time Frame

Baseline; Week 24, Week 48, Withdrawal/Completion

Title

Spleen Measurements as Assessed by Abdominal Ultrasound With Doppler During Follow-up Period After Part 2

Description

Time Frame

FU Week 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

74 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subject is able to understand and comply with protocol requirements and instructions and is likely to complete the study as planned, as well as provided a written consent. A subject age between ≥20 and <75 years at time of informed consent. A subject who applies to one of the following: Female subject with non-childbearing potential [i.e., physiologically incapable of becoming pregnant, who: has had a hysterectomy, or had a bilateral oophorectomy (ovariectomy), or had a bilateral tubal ligation, or is post-menopausal for greater than one year]. Female subject with childbearing potential, has a negative urine or serum pregnancy test at screening and within the 24-hour period prior to the first dose of SB-497115-GR, and completely abstains from intercourse or agree to use two of the following acceptable methods of contraception for 14 days before exposure to SB-497115-GR, throughout the clinical trial, and for 24 weeks after completion or premature discontinuation from the study. Intrauterine device or intrauterine system that meets the effectiveness criteria as stated in the product label. Male partner sterilization prior to the female subject's entry into the study, and this male is the sole partner for that subject. Double-barrier contraception (condom with spermicidal jelly, or diaphragm with spermicide). Male subject with childbearing potential partner completely abstains from intercourse or agree to use condom and diaphragm with spermicide. Subjects who were diagnosed as hepatitis C or compensated liver cirrhosis (Child-Pugh class A) without hepatic encephalopathy, or ascites. If there is a clear cirrhosis, treatment should be given with care as there is a potential of progressing to liver failure. Subjects who, in the opinion of the investigator, are appropriate candidates for Peg-IFN and RBV combination therapy for 48 weeks. HCV positive by TaqMan test at screening. Subject who fulfil all the organ functions below. Items Values Platelet <80,000 /μL Haemoglobin ≥12.0 g/dL* Absolute neutrophil count (ANC) ≥1500 /μL* Creatinine clearance >50 mL/minute Total bilirubin <2.0 mg/dL Albumin >3.0 g/dL Prothrombin time >60% *If the investigators consider the values are sufficient to give Peg-IFN/RBV, then a subject can be enrolled upon consulting the Medical Monitor. Exclusion Criteria: Subject who relapsed or did not respond after 48 weeks of Peg-IFN/RBV therapy had been given with sufficient dose previously. Subject with history of IFN (including Peg-IFN) therapy or Peg-IFN/RBV therapy, but could not been treated with optimal Peg-IFN/RBV therapy due to the reasons other than thrombocytopenia. Subject who received IFN therapy (including Peg-IFN), antiviral therapy (excluding oseltamivir phosphate, etc.), immuno-modulatory treatment, radiotherapy or phlebotomy within 3 months (90 days) prior to the first dose of SB-497115-GR. Treatment with an investigational drug within 30 days prior to the first dose of SB-497115-GR or 5 half-lives of that investigational drug (whichever is longer). Subject with decompensated liver disease. Chronic liver disease other than chronic hepatitis C (e.g., autoimmune hepatitis, alcohol-induced hepatitis, drug-induced hepatitis, etc.). Subject with idiopathic thrombocytopenic purpura or active autoimmune disease. Subject who have had a malignancy diagnosed and/or treated within the past 5 years. Subjects who require endoscopic treatment for varices or documented history of clinically significant bleeding from oesophageal or gastric varices. Any disease condition associated with active bleeding or requiring anticoagulation with heparin or warfarin. Subject with serious cardiac, cerebrovascular, chronic pulmonary disease or interstitial lung disease, or documented history of any of these diseases. Pre-existing cardiac disease (congestive heart failure in New York Heart Association Grade III/IV), or arrhythmias known to involve the risk of thromboembolic events (e.g. atrial fibrillation), or subjects with a QTcF >450 msec or if with bundle brunch block, QTcF >480 msec. Subject with depression, psychiatric disorder requiring treatment or suicidal ideation or suicide attempt history, or history of these. Subject with uncontrolled hypertension (≥160 mmHg systolic or ≥100 mmHg diastolic). Subject with diabetes mellitus that can not be controlled by treatment. Thyroid dysfunction not adequately controlled. Subjects with haemoglobinopathies. History or current condition of seizure disorder. Subject who was positive for Human Immunodeficiency Virus (HIV) antibody or Hepatitis B Virus (HBV) antigen. Subject with arterial or venous thrombosis history or evidence of portal vein thrombosis on abdominal imaging (e.g., by computerized tomography or magnetic resonance imaging) within 3 months. History of alcohol/drug abuse or dependence. History of platelet clumping that prevents reliable measurement of platelet counts. Subjects planning to have cataract surgery. History of major organ transplantation. Known hypersensitivity to SB-497115-GR ingredients, IFN (including Peg-IFN), nucleoside analogues or biological agents (i.e., vaccines). Pregnant or nursing women or a male subject with pregnant partner.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

GSK Clinical Trials

Organizational Affiliation

GlaxoSmithKline

Official's Role

Study Director

Facility Information:

Facility Name

GSK Investigational Site

City

Aichi

ZIP/Postal Code

467-8602

Country

Japan

Facility Name

GSK Investigational Site

City

Fukui

ZIP/Postal Code

918-8503

Country

Japan

Facility Name

GSK Investigational Site

City

Fukuoka

ZIP/Postal Code

803-8505

Country

Japan

Facility Name

GSK Investigational Site

City

Fukuoka

ZIP/Postal Code

830-0011

Country

Japan

Facility Name

GSK Investigational Site

City

Gunma

ZIP/Postal Code

370-0829

Country

Japan

Facility Name

GSK Investigational Site

City

Hyogo

ZIP/Postal Code

663-8501

Country

Japan

Facility Name

GSK Investigational Site

City

Ibaraki

ZIP/Postal Code

317-0077

Country

Japan

Facility Name

GSK Investigational Site

City

Kagawa

ZIP/Postal Code

760-0017

Country

Japan

Facility Name

GSK Investigational Site

City

Kagawa

ZIP/Postal Code

760-8557

Country

Japan

Facility Name

GSK Investigational Site

City

Kagoshima

ZIP/Postal Code

899-5112

Country

Japan

Facility Name

GSK Investigational Site

City

Kanagawa

ZIP/Postal Code

213-8587

Country

Japan

Facility Name

GSK Investigational Site

City

Nagasaki

ZIP/Postal Code

856-8562

Country

Japan

Facility Name

GSK Investigational Site

City

Oita

ZIP/Postal Code

879-5593

Country

Japan

Facility Name

GSK Investigational Site

City

Osaka

ZIP/Postal Code

540-0006

Country

Japan

Facility Name

GSK Investigational Site

City

Tokyo

ZIP/Postal Code

105-8470

Country

Japan

Facility Name

GSK Investigational Site

City

Wakayama

ZIP/Postal Code

646-8558

Country

Japan

12. IPD Sharing Statement

Citations:

PubMed Identifier

31258695

Citation

Kawaguchi T, Komori A, Fujisaki K, Nishiguchi S, Kato M, Takagi H, Tanaka Y, Notsumata K, Mita E, Nomura H, Shibatoge M, Takaguchi K, Hattori T, Sata M, Koike K. Eltrombopag enables initiation and completion of pegylated interferon/ribavirin therapy in Japanese HCV-infected patients with chronic liver disease and thrombocytopenia. Exp Ther Med. 2019 Jul;18(1):596-604. doi: 10.3892/etm.2019.7616. Epub 2019 May 24.

Results Reference

derived

Learn more about this trial

Japanese Phase II Study of SB-497115-GR in Hepatitis C Virus Infected Patients

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Japanese Phase II Study of SB-497115-GR in Hepatitis C Virus Infected Patients

Hepatitis C, Chronic

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial